title: Reduced haemodynamic coupling and exercise are associated with vascular stiffening in pulmonary arterial hypertension.
abstract: Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH.
  
  
  
  Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z0), characteristic impedance (ZC, a measure of proximal PA stiffness) and proximal and distal PA compliance (CPA).
  
  
  
  In patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (ZC=2.31±0.38 vs 1.33±0.15 WU×m2at rest; p=0.003) and PA compliance was decreased (CPA=0.88±0.10 vs 1.32±0.17 mL/mm Hg/m2at rest; p=0.0002). Z0did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p<10-6). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited CPAreduction at maximum exercise.
  
  
  
  In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z0results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor haemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated.
authors: Department of Biomedical, Chemical and Materials Engineering, San Jose State University, San Jose, California, USA.
authors: Alessandro
authors: A
authors: Bellofiore
authors: Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors: Eric
authors: E
authors: Dinges
authors: Department of Cardiology, Erasme University Hospital, Brussels, Belgium.
authors: Robert
authors: R
authors: Naeije
authors: Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Hamorabi
authors: H
authors: Mkrdichian
authors: Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Lauren
authors: L
authors: Beussink-Nelson
authors: Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors: Melissa
authors: M
authors: Bailey
authors: Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, Illinois, USA.
authors: Michael J
authors: MJ
authors: Cuttica
authors: Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Ranya
authors: R
authors: Sweis
authors: Division of Pulmonary and Critical Care Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors: James R
authors: JR
authors: Runo
authors: Department of Cardiology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors: Jon G
authors: JG
authors: Keevil
authors: Department of Radiology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors: Christopher J
authors: CJ
authors: Francois
authors: Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.|Feinberg Cardiovascular Research Institute, Northwestern University, Chicago, Illinois, USA.
authors: Sanjiv J
authors: SJ
authors: Shah
authors: Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA.|Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors: Naomi C
authors: NC
authors: Chesler
mesh_terms: D000328:Adult; D000368:Aged; D062186:Arterial Pressure; D006328:Cardiac Catheterization; D002641:Chicago; D015150:Echocardiography, Doppler; D025401:Echocardiography, Stress / Q000379:methods; D015444:Exercise; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000503:physiopathology*; D014655:Vascular Resistance; D059289:Vascular Stiffness; D016278:Ventricular Function, Right; D014922:Wisconsin