title: Prognostic relevance of changes in exercise test variables in pulmonary arterial hypertension.
abstract: BACKGROUND
  Exercise variables determined in patients with pulmonary arterial hypertension (PAH) at the time of diagnosis, predict survival. It is unknown whether upon treatment, subsequent changes in these exercise variables reflect improvements in survival. The aim of this study was to determine changes in exercise variables in PAH patients and to relate these changes to survival.
  
  
  METHODS
  Baseline cardiopulmonary exercise test (CPET) variables and six-minute-walk-distance (6MWD) were available from 65 idiopathic PAH patients (50 females; mean age 45±2yrs). The same variables were determined after treatment (13months) in a sub group of 43 patients. To estimate the association between changes in exercise variables and changes in cardiac function, right-ventricle ejection fraction (RVEF) was measured by cardiac MRI at baseline and after treatment in 34 patients. Mean follow-up time after the second CPET was 53 (range: 4-111) months. Kaplan-Meier analysis was used to relate survival to baseline and treatment-associated changes in exercise variables.
  
  
  RESULTS
  Survivors showed a significantly greater change in maximal oxygen uptake than non-survivors and this change in aerobic capacity was significantly related to changes in RVEF. From baseline until the end of the study period, two patients underwent a lung transplantation and 19 patients died. Survival analysis showed that baseline 6MWD (p<0.0001), maximal heart rate (p<0.0001) and the slope relating ventilation with carbon dioxide production (p≤0.05) were significant predictors of survival, whereas baseline oxygen uptake and oxygen pulse held no predictive value. Treatment associated changes in 6MWD (p<0.01), maximal heart rate (p<0.05), oxygen uptake (p<0.001) and oxygen pulse predicted survival (p<0.05), whereas changes in the slope relating ventilation with carbon dioxide production did not.
  
  
  CONCLUSIONS
  Exercise variables with prognostic significance when determined at baseline, retain their prognostic relevance after treatment. However, when changes in exercise variables upon treatment are considered, a different set of variables provides prognostic information.
authors.affiliation: Department of Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Herman
authors.initials: H
authors.lastname: Groepenhoff
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk-Noordegraaf
authors.forename: Mariëlle C
authors.initials: MC
authors.lastname: van de Veerdonk
authors.forename: Anco
authors.initials: A
authors.lastname: Boonstra
authors.forename: Nico
authors.initials: N
authors.lastname: Westerhof
authors.forename: Harm J
authors.initials: HJ
authors.lastname: Bogaard
mesh_terms: D000328:Adult; D005080:Exercise Test; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006339:Heart Rate; D006801:Humans; D006976:Hypertension, Pulmonary / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010101:Oxygen Consumption; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D016896:Treatment Outcome; D016138:Walking
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