Prognostic Relevance of Cardiopulmonary Exercise Testing in Low-Risk Pulmonary Arterial Hypertension

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Combinations of VO2 and change in CI during follow-up visits are valuable prognosis markers in low-risk patients with PAH.

Combinations of baseline peak oxygen uptake (VO2) and change in cardiac index (ΔCI) during follow-up visits are valuable markers of prognosis in low-risk patients with idiopathic, heritable, and drug-induced pulmonary arterial hypertension, according to a study published in The Journal of Heart and Lung Transplantation.

Investigators evaluated a derivation cohort of 80 consecutive idiopathic, heritable, and drug-induced pulmonary arterial hypertension cases between June 2006 and December 2009. Patients who were included had stable clinical condition for 1 year after diagnosis and institution of treatment and met the criteria of World Health Organization Functional Class I or II status, with no clinical signs of right heart failure, CI ≥2.5 liters/min/m2, no syncope, and right atrial pressure <8 mm Hg.

Patients were evaluated with a symptom-limited incremental cycle ergometer cardiopulmonary exercise testing with 10- to 15-Watt/min workload increments, with no patients receiving supplemental oxygen. Investigators analyzed VO2, carbon dioxide output, minute ventilation (VE), and end-tidal carbon dioxide partial pressure and monitored heart rate via 12-lead electrocardiography.

Peak work rate was defined as the highest level of exercise, and peak VO2 and peak VE were defined as the highest VO2 and VE that the participant could sustain for at least 15 seconds during the last stage of incremental exercise.

Patients were divided into 4 groups, based on VO2 peak and ΔCI: Group 1 (n=6) had a VO2 peak ≥15.7 mL/kg/min and a ΔCI ≥0.40; Group 2 (n=30) had a VO2 peak ≥15.7 mL/kg/min and a ΔCI <0.40; Group 3 (n=15) had a VO2 peak <15.7 mL/kg/min and a ΔCI ≥0.40; and Group 4 (n=29) had a VO2 peak <15.7 mL/kg/min and a ΔCI <0.40.

Diagnosis of pulmonary arterial hypertension relied on right heart catheterization showing precapillary pulmonary hypertension (mean pulmonary artery pressure ≥25 mm Hg, pulmonary artery wedge pressure ≤15 mm Hg); secondary causes were further excluded with the use of an algorithm incorporating respiratory function tests, perfusion lung scan, computer tomography scan, echocardiography, and laboratory tests.

Results showed that the combination of VO2 peak ≥15.7 mL/kg/min (≥60% predicted) and ΔCI ≥0.40 liter/min/m2 demonstrated high sensitivity (100%) and negative predictive value (100%) in recognizing patients at low risk of clinical worsening.

Pairwise comparison of patients in Groups 1 and 2 “had better prognosis compared with patients in Group 3 and 4” (Groups 1 vs 2 and Groups 3 vs 4 were not statistically significant; Groups 1 vs 3, =.0001; Groups 1 vs 4, =.0001; Groups 2 vs 3, =.001; Groups 2 vs 4, =.0001).

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This study was limited by a design that was monocentric and limited in size and was potentially limited by having only ΔCI measured as the invasive hemodynamic variable of predictive impact.

Researchers conclude that cardiopulmonary exercise testing “is a relevant addition to right heart catheterization to assess [pulmonary arterial hypertension] patients who are clinically improved and stabilized 1 year after institution of targeted therapies.”

Disclosure: Multiple authors declare affiliations with the pharmaceutical industry. Please refer to reference for a complete list of authors’ disclosures.


Badagliacca R, Papa S, Poscia R, et al. The added value of cardiopulmonary exercise testing in the follow-up of pulmonary arterial hypertension [published online December 7, 2018]. J Heart Lung Transplant. doi:10.1016/j.healun.2018.11.015