title: Central cardiac limit to aerobic capacity in patients with exertional pulmonary venous hypertension: implications for heart failure with preserved ejection fraction.
abstract: BACKGROUND
  The mechanism of functional limitation in heart failure with preserved ejection fraction remains controversial. We examined the contributions of central cardiac and peripheral mechanisms and hypothesized that the pulmonary vascular response to exercise is an important determinant of aerobic capacity among patients with exertional pulmonary venous hypertension (ePVH).
  
  
  RESULTS
  We compared 31 ePVH patients (peak VO2<80% of predicted and peak pulmonary arterial wedge pressure≥20 mm Hg) with 31 age- and sex-matched controls (peak VO2>80% predicted) who underwent invasive cardiopulmonary exercise testing for unexplained exertional intolerance. ePVH patients had lower peak cardiac output (73±14% versus 103±18% predicted; P<0.001) compared with controls, related both to impaired chronotropic response (peak heart rate 111±25 beats per minute versus 136±24 beats per minute; P<0.001) and to reduced peak stroke volume index (47±10 mL/min per m(2) versus 54±15 mL/min per m(2); P=0.03). Peak systemic O2 extraction was not different between groups (arterial-mixed venous oxygen content difference: 13.0±2.1 mL/dL versus 13.4±2.4 mL/dL; P=0.46). ePVH patients had higher resting (150±74 versus 106±50 dyne/s per cm(-5); P=0.009), peak (124±74 dyne/s per cm(-5) versus 70±41 dyne/s per cm(-5); P<0.001), and isoflow pulmonary vascular resistance (124±74 dyne/s per cm(-5) versus 91±33 dyne/s per cm(-5) at cardiac output≈10.6 L/min; P=0.04). Pulmonary vascular resistance decreased with exercise in all control subjects but increased in 36% (n=11) of ePVH patients. Abnormal pulmonary vascular response was not associated with peak VO2.
  
  
  CONCLUSIONS
  Reduced cardiac output response, rather than impaired peripheral O2 extraction, constrains oxygen delivery and aerobic capacity in ePVH. Pulmonary vascular dysfunction is common in patients with ePVH at rest and during exercise.
authors.affiliation: From the Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, Porto, Portugal (M.S.); Pulmonary and Critical Care Medicine (J.T., A.B.W., D.M.S.) and Division of Cardiovascular Medicine (A.R.O., A.M.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Cardiology, Boston Children's Hospital, MA (A.R.O.).
authors.forename: Mário
authors.initials: M
authors.lastname: Santos
authors.affiliation: From the Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, Porto, Portugal (M.S.); Pulmonary and Critical Care Medicine (J.T., A.B.W., D.M.S.) and Division of Cardiovascular Medicine (A.R.O., A.M.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Cardiology, Boston Children's Hospital, MA (A.R.O.).
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Opotowsky
authors.affiliation: From the Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, Porto, Portugal (M.S.); Pulmonary and Critical Care Medicine (J.T., A.B.W., D.M.S.) and Division of Cardiovascular Medicine (A.R.O., A.M.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Cardiology, Boston Children's Hospital, MA (A.R.O.).
authors.forename: Amil M
authors.initials: AM
authors.lastname: Shah
authors.affiliation: From the Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, Porto, Portugal (M.S.); Pulmonary and Critical Care Medicine (J.T., A.B.W., D.M.S.) and Division of Cardiovascular Medicine (A.R.O., A.M.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Cardiology, Boston Children's Hospital, MA (A.R.O.).
authors.forename: Julie
authors.initials: J
authors.lastname: Tracy
authors.affiliation: From the Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, Porto, Portugal (M.S.); Pulmonary and Critical Care Medicine (J.T., A.B.W., D.M.S.) and Division of Cardiovascular Medicine (A.R.O., A.M.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Cardiology, Boston Children's Hospital, MA (A.R.O.).
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Waxman
authors.affiliation: From the Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Unit, Faculty of Medicine, University of Porto, Porto, Portugal (M.S.); Pulmonary and Critical Care Medicine (J.T., A.B.W., D.M.S.) and Division of Cardiovascular Medicine (A.R.O., A.M.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Cardiology, Boston Children's Hospital, MA (A.R.O.). dsystrom@partners.org.
authors.forename: David M
authors.initials: DM
authors.lastname: Systrom
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D002302:Cardiac Output / Q000502:physiology*; D015444:Exercise / Q000502:physiology*; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D005082:Physical Exertion; D011652:Pulmonary Circulation / Q000502:physiology; D011659:Pulmonary Gas Exchange; D013318:Stroke Volume; D014655:Vascular Resistance
chemical_list: D000319:Adrenergic beta-Antagonists
keywords: exercise; heart failure; hemodynamics; pulmonary vascular resistance