title: Exercise pathophysiology and sildenafil effects in chronic thromboembolic pulmonary hypertension.
abstract: OBJECTIVE
  Symptoms in patients with chronic thromboembolic pulmonary hypertension (CTEPH) predominantly occur during exercise, while haemodynamic assessment is generally performed at rest. We hypothesised that exercise imaging of RV function would better explain exercise limitation and the acute effects of pulmonary vasodilator administration than resting measurements.
  
  
  METHODS
  Fourteen patients with CTEPH and seven healthy control subjects underwent cardiopulmonary testing to determine peak exercise oxygen consumption (VO2peak) and ventilatory equivalent for carbon dioxide (VE/VCO2) at the anaerobic threshold. Subsequently, cardiac MRI was performed at rest and during supine bicycle exercise with simultaneous invasive measurement of mean pulmonary arterial pressure (mPAP) before and after sildenafil.
  
  
  RESULTS
  During exercise, patients with CTEPH had a greater increase in the ratio of mPAP relative to cardiac output (CO) than controls (6.7 (5.1-8.7) vs 0.94 (0.86-1.8) mm Hg/L/min; p < 0.001). Stroke volume index (SVi) and RVEF increased during exercise in controls, but not in patients with CTEPH (interaction p < 0.001). Sildenafil decreased the mPAP/CO slope and increased SVi and RVEF in patients with CTEPH (p < 0.05) but not in controls. In patients with CTEPH, RVEF reserve correlated moderately with VO2peak (r = 0.60; p = 0.030) and VE/VCO2 (r = -0.67; p = 0.012). By contrast, neither VO2peak nor VE/VCO2 correlated with resting RVEF.
  
  
  CONCLUSIONS
  Exercise measures of RV function explain much of the variance in the exercise capacity of patients with CTEPH while resting measures do not. Sildenafil increases SVi during exercise in patients with CTEPH, but not in healthy subjects.
authors: Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium University Hospitals Leuven, Leuven, Belgium.
authors: Guido
authors: G
authors: Claessen
authors: Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium St Vincent's Hospital, University of Melbourne, Fitzroy, Australia.
authors: Andre
authors: A
authors: La Gerche
authors: Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium University Hospitals Leuven, Leuven, Belgium.
authors: Jean-Yves
authors: JY
authors: Wielandts
authors: University Hospitals Leuven, Leuven, Belgium Department of Imaging & Pathology, University of Leuven, Leuven, Belgium.
authors: Jan
authors: J
authors: Bogaert
authors: Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium University Hospitals Leuven, Leuven, Belgium.
authors: Johan
authors: J
authors: Van Cleemput
authors: University Hospitals Leuven, Leuven, Belgium Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors: Wim
authors: W
authors: Wuyts
authors: Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors: Piet
authors: P
authors: Claus
authors: University Hospitals Leuven, Leuven, Belgium Department of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors: Marion
authors: M
authors: Delcroix
authors: University of Hasselt and Heart Center, Jessa Hospital, Hasselt, Belgium.
authors: Hein
authors: H
authors: Heidbuchel
mesh_terms: D002908:Chronic Disease; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test / Q000379:methods; D005260:Female; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption; D010879:Piperazines / Q000627:therapeutic use*; D011655:Pulmonary Embolism / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects*; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use; D016278:Ventricular Function, Right / Q000502:physiology
chemical_list: D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate